Abstract：
Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared to younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNA (miRNA) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11M/7F, 66±1y) who underwent 3x/wk RT for 30 weeks [e.g., high intensity 3x/wk (HHH, n = 9) or alternating high-low-high intensity (HLH, n = 9)], after a standardized four-week wash-in. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using Weighted Gene Correlation Network Analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change (as measured by DXA). While no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT in order to maximize skeletal muscle mass accrual in older adults.
摘要：
阻力训练（RT）仍然是与年龄相关的肌肉质量下降的最有效治疗方法。然而,与年轻人相比，许多老年人对RT的反应肌肉肥大减弱。这可能归因于潜在的分子过程，这些过程因衰老而失调，并因不正确规定的每周RT体积而加剧。强度,和/或频率剂量。微小RNA（miRNA）是影响细胞内信号通路和蛋白质表达的关键表观遗传调节因子。是动态的，对运动刺激有反应，并且经常在疾病中失调。在这项研究中,我们使用非靶向miRNA-seq检测老年人骨骼肌和血清来源的外泌体中的miRNA(n=18,11M/7F,66±1y)接受3x/wkRT30周的患者[例如，高强度3x/wk（HHH，n=9)或交替的高-低-高强度(HLH，n=9)]，在标准化的四周清洗后。在每个组织中，使用加权基因相关网络分析(WGCNA)基于成对相关性将miRNA聚集到模块中。测试模块与RT诱导的大腿瘦体重(TLM)变化(如通过DXA测量)的幅度的关联。虽然没有模块是训练剂量独有的，我们在骨骼肌中鉴定了与TLM增加相关的miRNA模块,而与运动剂量无关.利用miRNA-靶标相互作用，我们分析了重要模块中的关键miRNA在生物学通路中的潜在调控作用.研究结果指向潜在的miRNA，这些miRNA可能是提供信息的生物标志物，也可以被评估为潜在的治疗靶标，作为RT的佐剂，以最大化老年人的骨骼肌质量积累。
